Protoporhyrin IX ferrochelatase (protoheme ferrolyase, E.C. 4.99.1.1; hereafter referred to as ferrochelatase), the terminal enzyme of the heme biosynthetic pathway, catalyzes the insertion of ferrous iron into protoporphyrin IX to yield protoheme. Distortion of the porphyrin macrocycle has long been recognized to be a critical step in porphyrin metallation. Porphyrin distortion heightens metal chelation by endowing porphyrin with an appropriate configuration for metal ion complexation. In this configuration, the lone-pair orbitals of the pyrrole nitrogens are exposed to the incoming metal ion.
Protoporhyrin IX ferrochelatase catalyzes the terminal step of the heme biosynthetic pathway by inserting ferrous iron into protoporphyrin IX. N-methyl protoporphyrin (NMPP), a transition-state analog and potent inhibitor of ferrochelatase, is commonly used to induce heme deficiency in mammalian cell cultures.